反应详情

A suspension of 7.07 g (21.3 mmol) of (S)-8-chloro-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxamidoxime in 50 ml of N,N-dimethylformamide was treated with 4.0 g (23.4 mmol) of chloroacetic anhydride. The yellow solution obtained was stirred at 105° for 2 hrs. and then completely freed from the solvents. The oily product was chromatographed over silica gel with methylene chloride/methanol 9:1 as the eluent and the oily product obtained was recrystallized from ethyl acetate/ether. The mother liquor was concentrated, the residue was again chromatographed over silica gel with acetonitrile as the eluent and the additional portion of product obtained was recrystallized from ethyl acetate/ether. There were obtained a total of 6.27 g (75%) of (S)-8-chloro-1-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one as white crystals; m.p. 184°-186° and [α]D20 =+36.1° (MeOH, c=1%).

1. customThe yellow solution obtained
2. customThe oily product was chromatographed over silica gel with methylene chloride/methanol 9:1 as the eluent
3. customthe oily product obtained
4. customwas recrystallized from ethyl acetate/ether
5. concentrationThe mother liquor was concentrated
6. customthe residue was again chromatographed over silica gel with acetonitrile as the eluent
7. customthe additional portion of product obtained
8. customwas recrystallized from ethyl acetate/ether